This renewal of our Aging Clinical Research Center (ACRC) reflects the continuing commitment of the Department of Psychiatry and Behavioral Sciences at Stanford to the study of Alzheimer's Disease (AD). The structure of the Center has been that of an "enabling center" or "core center" designed to facilitate the development of independent research projects using the Center's core resources in a more efficient manner than if they were replicated over a number of independent projects. We feel that we have been successful in this endeavor, fostering a major increase in funded AD research at Stanford, while at the same time minimizing the burden of patient participation in research. Our plan for the future is to continue along this successful track and to emphasize recent advances in certain areas of AD research, especially neurochemistry and genetics. Throughout the life of the Center, its theme has been the heterogeneity of AD. In particular, we have been impressed by the wide variability in the clinical manifestations and clinical course of the illness. For example, decline of our patients, in terms of percentage of total Mini-Mental State Exam (MMSE) or Alzheimer's Disease Assessment Scale (ADAS) score lost per year, ranges from nearly no change to over 25% decline. What is the basis of this variability of rate of decline? This is one question we have continued to address using an increasingly sophisticated set of methodological and biostatistical tools. In this application, we plan to further a strengthening of our Biostatistical Core by increasing the availability of senior investigators committed to the development of methodological tools we need to answer this difficult question.